About

David G. Drubin is the Ernette Comby Chair in Microbiology and a Professor of Cell Biology, Development and Physiology at the University of California, Berkeley. His research description can be found at http://mcb.berkeley.edu/faculty/CDB/drubind.html and his laboratory's website is http://drubinbarneslab.berkeley.edu/. He is involved in the field of molecular and cell biology, with a focus on microbiology, cell biology, development, and physiology. Drubin's work contributes to understanding cellular processes and microbiological mechanisms, although specific details of his research focus are not provided in the page text.

Research topics

• Computer Science
• Nanotechnology
• Biophysics
• Artificial Intelligence
• Materials science
• Cell biology
• Biology
• Physics
• Biochemistry
• Optics

Selected publications

• Polarized anionic phospholipids and exocytosis are implicated in the polarized recruitment of budding yeast AP180, an endocytic initiator

  Molecular Biology of the Cell · 2026-04-08

  articleSenior author

  Understanding of the mechanisms that initiate clathrin-mediated endocytosis (CME) is incomplete. Recent studies in budding yeast identified the endocytic adaptor proteins Yap1801/Yap1802 (budding yeast AP180) as key CME factors that promote CME initiation in daughter cells during polarized growth, but how Yap1801/2 are recruited preferentially to the plasma membrane of daughter cells is not clear. The only known cargos for Yap1801/2 in yeast are the synaptobrevins Snc1 and Snc2, which serve as v-SNARES for exocytic vesicles reaching the plasma membrane and are crucial for polarized cell growth. In this study, we examine the spatiotemporal dynamics of functional, fluorescent protein-tagged Snc2 expressed from its endogenous locus and provide evidence that, along with anionic phospholipids, Snc2 specifically recruits Yap1802 to growing daughter cells. This protein-protein interaction creates a direct link between polarized secretion and CME and has further implications in CME initiation.

  PublisherDOI

• Class-I myosin responds to changes in membrane tension during clathrin-mediated endocytosis in human induced pluripotent stem cells

  Proceedings of the National Academy of Sciences · 2026-02-24 · 1 citations

  articleOpen accessSenior authorCorresponding

  Clathrin-mediated endocytosis (CME) is an essential cellular process that needs to operate efficiently across a wide range of conditions. Internalization of the endocytic site involves forces generated by membrane-bound proteins and Arp2/3-mediated branched actin filament assembly to bend the plasma membrane from flat to omega-shaped. In mammalian CME, the requirement for a branched actin filament network varies depending on cell type and differences in membrane tension. However, how the actin network adapts to changes in load in order to ensure robustness of this process over a range of membrane tensions is not understood. Here, we combine live-cell imaging and superresolution microscopy of genome-edited human induced pluripotent stem cells to investigate the role of the mammalian class-I myosin, Myosin1E (Myo1E), in load adaptation. Under normal conditions, sites that recruit Myo1E are rare and exhibit slow CME dynamics. However, as membrane tension increases and CME dynamics are slowed globally, Myo1E is recruited to more sites, likely to increase actin assembly and motor activity, resulting in increased force generation to rescue stalled sites and promote internalization. Loss of Myo1E results in increased Arp2/3 complex lifetime at CME sites under normal conditions, and at high membrane tension, these sites fail to recruit as many Arp2/3 molecules. We propose that Myo1E is recruited to CME sites that have stalled due to increased membrane tension, where it helps build a more effective branched actin network by generating force through motor activity and recruiting additional Arp2/3 complexes to rescue stalled sites.

  PublisherDOI

• BPS2026 – A FRET-based molecular tension sensor reveals actin-driven force dynamics in clathrin-mediated endocytosis

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Force-insensitive myosin-I enhances endocytosis robustness through actin network-scale collective ratcheting

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-09

  preprintOpen access

  Abstract Force production by Type-I myosins influences endocytic progression in many cell types. Since different myosin-I isoforms exhibit distinct force-dependent kinetic properties, it is important to investigate how these properties affect endocytic outcomes, and the mechanisms through which myosin-I contributes to endocytosis. To this end, we adapted our agent-based simulations of endocytic actin networks and incorporated nonprocessive, single-headed myosin motors at the base of the endocytic pit. We varied the unbinding rate and the force dependence of myosin unbinding. Our results revealed that the inclusion of myosin motors facilitated endocytic internalization, but only under kinetic regimes with rapid and less force-sensitive unbinding. Conversely, slow or strongly force-dependent unbinding impeded endocytic progression. As membrane tension increased, the boundary between assistive and inhibitory phases shifted, allowing the myosins to assist over larger regions of the kinetic landscape. Myosin-I’s contribution to internalization could not be explained by direct force transduction or increased actin assembly. Instead, the myosins collectively bolstered the robustness of internalization by limiting pit retraction. Significance Statement Type-I myosins with varying force sensitivity levels participate in different membrane deformation pathways, but the mechanistic link between molecular biophysical properties and cellular function remains poorly understood. The authors analyze a computational model of endocytosis with type-I myosins and find that myosins with lower force sensitivity assist endocytosis by reducing backsliding along the internalization trajectory, while myosins with higher force sensitivity stall endocytosis by sequestering actin in non-productive orientations. These results introduce a new perspective on the function of type-I myosins in membrane reshaping: as a collective emergent property rather than the sum of individual force-generating motors.

  PublisherOA PDFDOI

• Class-I myosin responds to changes in membrane tension during clathrin-mediated endocytosis in human induced pluripotent stem cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-13 · 1 citations

  preprintSenior authorCorresponding

  Clathrin-mediated endocytosis (CME) is an essential cellular process that needs to operate efficiently across a wide range of conditions. Internalization of the endocytic site involves forces generated by membrane-bound proteins and Arp2/3-mediated branched actin filament assembly to bend the plasma membrane (PM) from flat to omega-shaped. In mammalian CME, the requirement for a branched actin filament network varies depending on cell type and differences in membrane tension. However, how the actin network adapts to changes in load in order to ensure robustness of this process over a range of membrane tensions is not understood. Here, we combine live-cell imaging and super-resolution microscopy of genome-edited human induced pluripotent stem cells (hiPSCs) to investigate the role of the mammalian class-I myosin, Myosin1E (Myo1E), in load adaptation. Under normal conditions, sites that recruit Myo1E are rare and exhibit slow CME dynamics. However, as membrane tension increases and CME dynamics are slowed globally, Myo1E is recruited to more sites, likely to assemble more branched actin, resulting in increased force generation to rescue stalled sites and promote internalization. Loss of Myo1E results in increased Arp2/3 complex lifetime at CME sites under normal conditions, and at high membrane tension, these sites fail to recruit as many Arp2/3 molecules. We propose that Myo1E is recruited to CME sites that have stalled due to increased membrane tension, where it helps build a more effective branched actin network by generating force through motor activity and recruiting additional Arp2/3 complexes to rescue stalled sites. Significance: For mammalian cells to internalize extracellular cargo via clathrin-mediated endocytosis (CME), specific regions of the plasma membrane (PM) must bend from flat to inwardly curved, a process that requires force-generating proteins. One key component in generating this force during CME is the branched actin network, in which actin filaments polymerize against the plasma membrane. When PM tension increases, more force is required to generate curvature, prompting the assembly of actin and actin associated proteins to aid the process. We demonstrate that the class-I myosin motor, Myosin1E (Myo1E), becomes increasingly crucial as membrane tension rises, presumably to build a more effective branched actin network to facilitate internalization of slowed sites.

  PublisherDOI

• Force-insensitive myosin-I enhances endocytosis robustness through actin network–scale collective ratcheting

  Molecular Biology of the Cell · 2025-05-28 · 3 citations

  article

  Force production by type-I myosins influences endocytic progression in many cell types. Because different myosin-I isoforms exhibit distinct force-dependent kinetic properties, it is important to investigate how these properties affect endocytic outcomes, and the mechanisms through which myosin-I contributes to endocytosis. To this end, we adapted our agent-based simulations of endocytic actin networks and incorporated nonprocessive, single-headed myosin motors at the base of the endocytic pit. We varied the unbinding rate and the force dependence of myosin unbinding. Our results revealed that the inclusion of myosin motors facilitated endocytic internalization, but only under kinetic regimes with rapid and less force-sensitive unbinding. Conversely, slow or strongly force-dependent unbinding impeded endocytic progression. As membrane tension increased, the boundary between assistive and inhibitory phases shifted, allowing the myosins to assist over larger regions of the kinetic landscape. Myosin-I's contribution to internalization could not be explained by direct force transduction or increased actin assembly. Instead, the myosins collectively bolstered the robustness of internalization by limiting pit retraction.

  PublisherDOI

• Clathrin-mediated endocytosis in budding yeast at a glance: animated

  Journal of Cell Science · 2025-11-15 · 1 citations

  article

  Clathrin-mediated endocytosis (CME) is an essential, highly conserved process in eukaryotic cells that facilitates the internalization of plasma membrane components, transmembrane proteins and extracellular nutrients. This complex pathway involves the concerted assembly and disassembly of many different proteins at the plasma membrane. Budding yeast has served as a powerful model for dissecting CME through combined genetic, biochemical, quantitative imaging and mathematical approaches. In this Cell Science at a Glance article, we integrate decades of quantitative data to generate a three-dimensional molecular animation depicting the full progression of CME in budding yeast (Movie 1). The animation and accompanying poster capture the spatial and temporal dynamics of key protein players. In addition, we highlight recent advances in understanding of the condensation of endocytic proteins into distinct sites and the organization of actin networks that generate the forces necessary to deform and internalize the membrane against the high internal turgor pressure of the budding yeast cell.

  PublisherDOI

• Fourier-based three-dimensional multistage transformer for aberration correction in multicellular specimens

  Nature Methods · 2025-10-01 · 1 citations

  articleOpen access

  High-resolution tissue imaging is often compromised by sample-induced optical aberrations that degrade resolution and contrast. Although wavefront sensor-based adaptive optics (AO) can measure these aberrations, such hardware solutions are typically complex, expensive to implement and slow when serially mapping spatially varying aberrations across large fields of view. Here we introduce AOVIFT (adaptive optical vision Fourier transformer)-a machine learning-based aberration sensing framework built around a three-dimensional multistage vision transformer that operates on Fourier domain embeddings. AOVIFT infers aberrations and restores diffraction-limited performance in puncta-labeled specimens with substantially reduced computational cost, training time and memory footprint compared to conventional architectures or real-space networks. We validated AOVIFT on live gene-edited zebrafish embryos, demonstrating its ability to correct spatially varying aberrations using either a deformable mirror or postacquisition deconvolution. By eliminating the need for the guide star and wavefront sensing hardware and simplifying the experimental workflow, AOVIFT lowers technical barriers for high-resolution volumetric microscopy across diverse biological samples.

  PublisherOA PDFDOI

• Fourier-Based 3D Multistage Transformer for Aberration Correction in Multicellular Specimens

  Research Square · 2025-04-02

  preprintOpen access
  PublisherDOI

• Harnessing fusion of genome-edited human stem cells to rapidly screen for novel protein functions in vivo

  Molecular Biology of the Cell · 2025-09-24

  articleSenior author

  Genome editing has enabled the integration of fluorescent protein coding sequences into genomes, resulting in expression of in-frame fusion proteins under the control of their natural gene regulatory sequences. While this technique overcomes the well-documented artifacts associated with gene overexpression for biological processes sensitive to altered protein stoichiometry, such as clathrin-mediated endocytosis (CME), editing genomes of metazoan cells incurs a significant time cost compared with simpler organisms, such as yeast. Editing two or more genes to express multiple fluorescent fusion proteins in a single cell line has proven to be a powerful strategy for uncovering spatial dynamic, and therefore functional, relationships among different proteins, but it can take many months to edit each gene within the same cell line. Here, by utilizing cell fusions, we quickly generated cells expressing pairwise permutations of fluorescent fusion proteins in genome-edited human cells to reveal previously undetected protein-organelle interactions. We fused human induced pluripotent stem cells (hiPSCs) that express in-frame fusions of CME and actin cytoskeleton proteins with hiPSCs that express fluorescently tagged organelle markers, uncovering novel interactions between CME proteins, branched actin filament networks, and lysosomes.

  PublisherDOI

Recent grants

• NIH Grant R01GM042759

  NIH · $3.6M · 2006

• Endocytic Functions for the Mammalian Actin Cytoskeleton

  NIH · $3.4M · 2002–2016

• Actin assembly and clathrin-mediated endocytosis in yeast and mammals

  NIH · $10.9M · 2016–2026

• Molecular Analysis of the Yeast Actin Cytoskeleton

  NIH · $4.0M · 1989–2016

• NIH Grant S10RR019290

  NIH · $491k · 2005

Frequent coauthors

• Georjana Barnes

  University of California, Berkeley

  51 shared

• John R. Yates

  Scripps Research Institute

  24 shared

• Yidi Sun

  University of California, Berkeley

  22 shared

• Avital A. Rodal

  Brandeis University

  22 shared

• Pekka Lappalainen

  University of Helsinki

  22 shared

• Johannes Schöneberg

  University of California, San Diego

  20 shared

• David C. Amberg

  SUNY Upstate Medical University

  17 shared

• Bruce L. Goode

  Brandeis University

  17 shared